Variations in Biodistribution and Acute Response of Differently Shaped Titania Nanoparticles in Healthy Rodents
Martina B. Violatto,
Giovanni Sitia,
Laura Talamini,
Annalisa Morelli,
Ngoc Lan Tran,
Qian Zhang,
Atif Masood,
Beatriz Pelaz,
Indranath Chakraborty,
Daxiang Cui,
Wolfgang J. Parak,
Mario Salmona,
Neus G. Bastús,
Victor Puntes,
Paolo Bigini
Affiliations
Martina B. Violatto
Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy
Giovanni Sitia
Experimental Hepatology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy
Laura Talamini
Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy
Annalisa Morelli
Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy
Ngoc Lan Tran
Experimental Hepatology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy
Qian Zhang
Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Institute of Nano Biomedicine and Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, China
Atif Masood
Karachi Institute of Radiotherapy and Nuclear Medicine (KIRAN), 75530 Karachi, Pakistan
Beatriz Pelaz
Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS), Departamento de Química Inorgánica, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Indranath Chakraborty
School of Nano Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India
Daxiang Cui
Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Institute of Nano Biomedicine and Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, China
Wolfgang J. Parak
Center for Hybrid Nanostructures (CHyN), Universität Hamburg, Luruper Chaussee 149, 22607 Hamburg, Germany
Mario Salmona
Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy
Neus G. Bastús
Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain
Victor Puntes
Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain
Paolo Bigini
Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy
Titanium dioxide nanoparticles (TiO2 NPs) are one of the main sources of the nanoparticulate matter exposure to humans. Although several studies have demonstrated their potential toxic effects, the real nature of the correlation between NP properties and their interaction with biological targets is still far from being fully elucidated. Here, engineered TiO2 NPs with various geometries (bipyramids, plates, and rods) have been prepared, characterized and intravenously administered in healthy mice. Parameters such as biodistribution, accumulation, and toxicity have been assessed in the lungs and liver. Our data show that the organ accumulation of TiO2 NPs, measured by ICP-MS, is quite low, and this is only partially and transiently affected by the NP geometries. The long-lasting permanence is exclusively restricted to the lungs. Here, bipyramids and plates show a higher accumulation, and interestingly, rod-shaped NPs are the most toxic, leading to histopathological pulmonary alterations. In addition, they are also able to induce a transient increase in serum markers related to hepatocellular injury. These results indicate that rods, more than bipyramidal and spherical geometries, lead to a stronger and more severe biological effect. Overall, small physico-chemical differences can dramatically modify both accumulation and safety.